Beta-thalassemia major results in ineffective erythropoiesis. The primary mechanism of anemia in beta-thalassemia is:

• A Excess free alpha-globin chains precipitating in erythroblasts, causing oxidative damage and intramedullary destruction ✓
• B Decreased alpha-globin synthesis causing insufficient hemoglobin A production
• C Iron overload causing mitochondrial damage in early erythroid precursors
• D Increased erythropoietin resistance due to chronic inflammation

Explanation

In beta-thalassemia major, deficient or absent beta-globin synthesis leads to an excess of free alpha-globin chains that are highly unstable and precipitate within developing erythroblasts. These alpha-chain inclusions generate reactive oxygen species (via heme-catalyzed Fenton reaction), causing membrane oxidation, cross-linking of spectrin, and destruction of erythroblasts within the marrow (ineffective erythropoiesis). This intramedullary hemolysis is the dominant mechanism — up to 70–80% of erythroblasts are destroyed before reaching the circulation. The few surviving RBCs are microcytic and hypochromic and undergo peripheral hemolysis in the spleen, compounding the anemia.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.